ORGANIC LETTERS
Remarkable Effect of a Silicon Group on the Stereoselectivity of Radical 5-exo-Trig Cyclizations
2004 Vol. 6, No. 3 325-328
Philippe James and Yannick Landais* UniVersite´ Bordeaux-I, Laboratoire de Chimie Organique et Organome´ tallique, 351, Cours de la Libe´ ration, 33405 Talence Cedex, France
[email protected] Received October 16, 2003
ABSTRACT
Sulfonyl radical mediated 5-exo-trig cyclization of chiral 3-silylhepta-1,6-dienes has been shown to provide cyclopentanes having up to four stereogenic centers with an unexpectedly high level of stereocontrol.
Five-membered-ring carbocycles are a common structural unit in natural products of biological interest and can be assembled in a number of ways (i.e. 1-2, Scheme 1).1 We
Scheme 1.
Natural Products Containing Cyclopentanes
recently started an investigation on the construction of polysubstituted cyclopentane skeletons of type 3, based on the cyclization of dienes 4 having a chiral allylsilane moiety. (1) (a) Herndon, J. W. Tetrahedron 2000, 56, 1257-1280. (b) Hartley, R. C.; Caldwell, S. T. J. Chem. Soc., Perkin Trans. 1 2000, 477-501. (c) Hassner, A.; Ghera, E.; Yechezkel, T.; Kleiman, V.; Balasubramanian, T.; Ostercamp, D. Pure Appl. Chem. 2000, 72, 1671-1683. 10.1021/ol036025v CCC: $27.50 Published on Web 01/13/2004
© 2004 American Chemical Society
Our strategy relied on a sequential tosyl radical addition, 5-exo-trig cyclization, β-fragmentation. This process is known to provide five-membered-ring skeletons under mild conditions with generally high efficiency.2 Excellent control of the C1-C2 relative configuration is usually observed but the control of the C2-C3 configuration has remained a challenging task to achieve.3 A few examples on the application of this strategy to the synthesis of heterocyclic analogues have been reported, effectively revealing that only low to moderate levels of stereocontrol could be attained.3 Recent studies on intermolecular radical functionalization of chiral allylsilanes, however, convinced us that a silicon group at the stereogenic center might be a decisive element for the stereocontrol in this radical process.4 So far, to our knowledge, this issue has not been addressed. We describe here our preliminary (2) (a) Bertrand, M.-P.; De Riggi, I.; Lesueur, C.; Gastaldi, S.; Nouguier, R.; Jaime, C.; Virgili, A. J. Org. Chem. 1995, 60, 6040-6045. (b) Wang, C.; Russell, G. A. J. Org. Chem. 1999, 64, 2346-2352. (c) Harvey, I. W.; Philips, E. D.; Whitham, G. H. Tetrahedron 1997, 53, 6493-6508. (d) Harvey, I. W.; Whitham, G. H. J. Chem. Soc., Perkin Trans. 1 1993, 185190. (e) Harvey, I. W.; Whitham, G. H. J. Chem. Soc., Perkin Trans. 1 1993, 191-196. (3) (a) Bertrand, M.-P.; Gastaldi, S.; Nouguier, R. Tetrahedron Lett. 1996, 37, 1229-1232. (b) Bertrand, M.-P.; Gastaldi, S.; Nouguier, R. Tetrahedron 1998, 54, 12829-12840. (c) Nouguier, R.; Gastaldi, S.; Stien, D.; Bertrand, M.-P.; Renaud, P. Tetrahedron Lett. 1999, 40, 3371-3374. (d) Denes, F.; Chemla, F.; Normant, J. F. Angew. Chem., Int. Ed. 2003, 47, 4043-4046.
results on the sulfonyl radical cyclizations of chiral allylsilanes such as 4, and demonstrate that this approach provides an efficient and highly stereocontrolled access to polysubstituted five-membered-ring carbocycles 3. Chiral racemic allylsilanes were easily prepared by using the following sequences. For instance, 1,6-diene 8 was prepared in 6 steps from allylsilane 5 (Scheme 2). Metalation
Scheme 2.
Preparation of Allylsilane 8
diastereomer anti-11,9 which was sulfonylated as above, affording the required allylic sulfone 12 in reasonable yield as a unique stereoisomer. We first investigated the radical cyclization by treating allylsilane 8 with a catalytic amount of p-TolSO2SePh in the presence of AIBN (Table 1, entry 1). A mixture of two
Table 1. Sulfonyl Radical Mediated 5-exo-Trig Cyclization of Dienes 8 and 12
entry
of 5 and coupling with oxetane afforded an inseparable 2:1 R/γ mixture5 of alcohols 6 which were directly oxidized into the corresponding aldehydes. Separation of the major aldehyde followed by Wittig-Horner olefination and reduction of the resulting R,β-unsaturated ester with DIBAH led to the allylic alcohol, which was protected as its acetate 7. Palladium-catalyzed sulfonylation6 of 7 finally led to the required (E)-allylic sulfone 8. A second model 12, having an additional stereogenic center, was prepared starting from vinylsilane 97 (Scheme 3). 9 was submitted to Johnson-Ireland rearrangement to provide the β-silylester 10.8 The enolate of 10 was then alkylated with (E)-1,4-dibromobut-2-ene to give a unique
Scheme 3.
Preparation of Allylsilane 12
1 2 3 4 5 6
diene 8 8 8 8 12 12
solvent
T (°C)
C6H6 C6H6 CCl4 CHCl3 CHCl3 CH2Cl2
80a 16 -15 -50b -50b -78c
time (h)
13/14d
yielde (%)
10 4 2.5 0.5 0.5 3.5
86:14 96:4 98:2 >99:99:
